Vitamin b6 intermediates



Patented June 17, 1947 UNITED STATES PATENT OFFICE VITAMIN Be INTERMEDIATES Stanton A. Harris, Westfield, N. J., 'assignor to of New Jersey Merck & 00., Inc., Rahway, N. J a corporation No Drawing. Application July 11, 1944,

Serial No. 544,471

18 Claims. 1

This application relates generally to a process for the preparation of novel chemical compounds;

in a particular sense it is concerned with the preparation of intermediates useful in the synthesis of vitamin Bo (2-methyl-3-hydroxy-4,5-dihydroxymethylpyridine). I

This application is a continuation-in-part of the copending application by the same inventor, Serial No. 267,603, filed April 18, 1939, entitled Synthesis of vitamin Ba intermediates and process for producing them.

The compounds forming the subject matter of the present invention are represented by the formula:

wherein R is an alkyl, aryl or aralkyl group. According to the present invention, these compounds are obtained by nitrating a compound of the formula:

CHaOR wherein R is as above. It is presently preferred to conduct this reactionin a solvent such as acetic anhydride or an equivalent organic liquid wherein the reactants and the reaction product are soluble and which is substantially inert'wiith.

respect to the nitrating agent used under the conditions of reaction. It is preferred to perform the reaction at temperatures less than about 100 C.

be understood that these examples are given by way of illustration and not of limitation.

Example 1 CHgOCzHs CHrOCzH C N HN 0 a N O C N (acetic CH: --O anhydride) 0 H: O i N N H H About g. of Y 3 cyano-4-ethoxymethyl-6- methyl-Z-pyridone (obtained by reacting ethoxyacetylacetone and cyano-acetamide) in 13 cc. of

' acetic anhydride is cooled and treated with 2.16

It will be understood by those versed in this x art that pyridones are equivalents of the corresponding hydroxy pyridine, for example:

onion crnoa ON ON on; =0 on on g N The following examples illustrate methods of carrying out the present invention, but it is to cc. of fuming nitric acid in 2 cc. of acetic anhydride, a little urea being added as a catalyst. The

solid gradually dissolves with evolution of heat. The reaction mixture is maintained at a. temperature below about 45 C. until the reaction is completed, as indicated by cessation of heat evolution. Upon pouring the mixture onto ice, crystallization of 3-cyano-4-ethoxymethyl-5-nitro-6- methyl-2-pyridone (M. P. 164-165 C.) takes place. The product is removed and purified by conventional operations.

Example 2 011.com, cnlocnm 0N F6(N0a)a NO ON --b (acetic OH 0 anhydride) 'CH O N N H n- To about 40 g. of 3-cyano-4- ethoxymethyl-6- .methyl-2-pyridone is added sufilcient acetic anhydride to form a paste, and the mixture heated to about C. To this mixture is added, with agitation, a solution of 60 g. of ferric nitrate What is claimed is: 1. A compound represented by the formula:

CHrOR NO ON on o N 11 wherein R is selected from the group consisting of alkyl, aryl and aralkyi.

2. A compound represented by the formula:

crnoa N CN CH O

wherein R is aliwl.

3. A compound represented by the formula:

CHlOR NO ON CH O wherein R is aryi.

4. A compound represented by the formula:

onion NOfIN on 0 wherein R is aralkyl.

5. A compound represented by the formula:

NO ON CH -O 6. The process which comprises reacting a com.- pound of the formula:

' RIG 0 wherein R is selected from the class consisting of alkyl, aryl and aralkyl groups with a nitrating agent in the presence of acetic anhydride to form a compound of the formula:

onion ON ON 4 10. The process which comprises reacting 3-cyano-4-ethoxymethylr6-methyl-2-pyridone with a nitrating agent in the presence of acetic anhy dride to form 3-cyano- 4-ethoxymethyl-5-nitro- 6-methy1-2-pyridone.

11. The process which comprises reacting a compound of the formula:

I omoa 0N HsCL O N H wherein R is selected from the class consisting of 'alkyl, aryl and aralkyl groups with fuming nitric acid in the presence of acetic anhydride to form a compound of the formula:

CHaOR OrN CN wherein R. is as above.

12. The process which comprises reacting 3-cyano-4-ethoxymethyl-6-methy1-2-pyridone with fuming nitric acid in the presence of acetic anhydride to form 3-cyano-4-ethoxymethy1-5-nitro-6-methyi-2-pyridone.'

13.The process which comprises reacting a compound of the formula:

CHrOR Hi0 O wherein R. is selected from the class consisting of alhvl, aryl, and araikyl groups with ferric nitrate in the presence of acetic anhydride to form a com- I pound of the formula:

CHaOR OsN CN wherein R is as above.

14. The process which comprises reacting 3- cyano-4-ethoxymethyl-6-methyl-2-pyridone with ferric nitrate in the presence of acetic anhydride to form 3-cyano-4-ethoxymethyl-5-nitro-6- methyl-Z-pyridone.

15. The process which comprises reacting 3- cyano-4-alkoxymethyl-6-methyl-2pyridone with fuming nitric acid in the presence of acetic anhydride to form 3-cyaho-4-alkoxymethyl-5-nitro-6-methyl-2-pyridone.

16. The process which comprises reacting B-cyano-4-aralkoxymethyl-6-methyl-2-pyridone with fuming nitric acid in the presence of acetic anhydride to form 3-cyano-4-aralkoxymethyl-S-nitro-6-methyl-2-pyridone.

17. The process which comprises reacting S-cyano-4-aralkoxymethyl-6-methyl-2-pyridone with ferric nitrate in the presence of acetic anhydride to form 3-cyano-4-aralkoxymethyl-5-nitro- 6-methy1-2-pyrldone.

18. The process which comprises reactin 3- cyano-4-alkoxymethyl-6-methy1-2-pmidone with ferric nitrate in the presence of acetic anhydride to form 3-cyano-4-a1koxymethyl-5-nitro-6- methyl-2-pyridone.

' STANTON A. HARRIS. 

